There’s a New Bug in Town
All the infectious news that’s fit to communicate
Feel free to skip the catchy name, Burkholdaria pseudomallei, a bacterium causing severe disease in humans (Melioidosis), and just found in the environment of the United States for the first time. Historically this organism, and the human disease it causes, has been limited to areas of Southeast Asian, and northern Australia, but in recent years it has been an emerging pathogen in South America. In the course of investigating two cases of Melioidosis in the United States, the CDC just reported that this bacteria was isolated from soil samples in Mississippi. This is an organism which is considered a potential bioterrorism threat, and has been studied as such for many years. The CDC was quick to report that this bacteria was not the same strain which had been involved with a “Lab Leak” at the National Primate Research Center at Tulane in 2014. That’s reassuring, but there is another take home message here. The National Primate Lab is a BSL-3 containment center, more secure and sophisticated than the Wuhan lab, yet an undisputed leak of this potential bioterrorism bacteria occurred there, killing monkeys in their colony which were not involved in any experiments with this agent. As you can imagine an exhaustive investigation was launched and no reason for the leak was ever found. Just remember the next time politicians, pundits, scientists, or the mob on Twitter tell you that you are not allowed to consider an avenue of thought whose on-ramp is marked by the sign Common Sense, “There are more things in heaven and earth than are dreamt of in your philosophy Horatio”.
This summer’s “slow burn” of COVID goes on unabated with the rock steady 6000+ new hospitalizations per day, and a daily death rate which seems to have plateaued below 500/day. We are told newly formulated vaccine boosters with a splash of Wuhan and a new dash of BA.4/.5 will be available by the end of next month. Pretty clear that their “efficacy” will be based on immuno-bridging (antibody levels generated) and not on clinical data of disease prevention or modification. What’s the best strategy to plan your future vaccination path? Anybody’s guess would be an honest answer and one you will never hear from the CDC. My guess is that almost everyone who has had 3 doses of RNA vaccine should wait for September—the exception to that would be severely immunocompromised people, who of course should be closely following the advice of their physician. If you had 3 doses of vaccine and a breakthrough infection a while back, that’s a clear signal to wait for the updated boosters. What if you had 3 doses and came down with BA.5 during the most recent wave of summer slow burn? Well, you just had a “booster” (perhaps more effective than what they will be dolling in out in September), and I would be in the watchful waiting mode while data accumulates on the new booster’s efficacy, side effects and the landscape of new variants when they emerge.
Paxlovid rebound is the media rage these days, and unfortunately I think it is giving this perfectly good therapeutic a bum rap for no good reason. This relatively low side effect drug was developed to prevent serious or fatal disease; it was never intended to make sure that every trace of the virus was eradicated at the tail end of an infection. It wasn’t intended to speed up your negative COVID test and be a “get out of Jail free card”. It also wasn’t developed to treat minor cold symptoms occurring in the presence of SARS2-Cov19. In my opinion that would include not treating those mild cold symptoms re-occurring after an initial course of Paxlovid. (shout out to Anthony) It’s efficacy was validated in high risk, unvaccinated people and it performed brilliantly. It is still active against all the COVID variants, and because we know certain vaccinated people are are high risk, because of variant evolution toward vaccine escape, it certainly makes sense to be treating high risk vaccinated folks. I can give you three good reasons why low risk people shouldn’t take it: no discernible benefit to the patient, overuse will shorten the time until resistance emerges, it costs society money and it’s your tax dollars. President Biden’s Paxlovid rebound, like Dr. Fauci’s is a clinically insignificant event. Although we don’t have the data yet, it’s a good bet this is much more common in the elderly, and reflective of the senescence of the immune system in octogenarians.
Next up is Monkeypox with it’s brand new declaration as a National Public Health Emergency. The government is responding now with a more coherent vaccine distribution plan, and people are eagerly lining up. In an attempt to address the shortage of available vaccine, the FDA has revealed that they are evaluating a plan to change the route of administration from the approved subcutaneous route to one fifth of the normal dose given into the skin. There are vaccines which were developed and tested by the intra-dermal route. If the FDA proceeds with this plan, let’s hope they at least structure trials and data collection to learn from what will be a very large experiment. Also I’d like to point out that there is a learning curve on intra-dermal injection. If there’s any interest we could start a pool to bet on how many 1/5 normal doses will end up being subcutaneous (and therefore sub-therapeutic) rather than intra-dermal, when tens of thousands of people who have never given this type of injection start banging away.
None of the 7,500 Monkeypox cases in the US have been fatal, but some people have had a fair amount of misery in the form of painful genital, oral and anal ulcers. There is a drug tecorvirimat (TPOXX), which is PRESUMED to be effective in treating human Monkeypox. As of July 22 only about 220 people in the US had been treated with this despite a huge supply of drug. Why would so few people be prescribed what appears to be a safe drug (at least in the normal human volunteer tests previously conducted)? The drug can only be obtained from the National Strategic Stockpile via the CDC. Until the National Public Health Emergency was declared on Wednesday, physicians working in a healthcare organization would need to have a treatment protocol approved by their Institutional Review Board. That hurdle has been lifted by the CDC now supplying a general approval through the Emergency declaration, but these are the remaining administrative requirements taken from the CDC website.
Required
Informed Consent Form [214KB, 5 pages]: Obtain prior to treatment.
Patient Intake Form [321KB, 3 pages]: Baseline assessment.
FDA Form 1572 [1MB, 2 pages]: One signed 1572 per facility suffices for all TPOXX treatments administered under the EA-IND at the same facility.
Clinical Outcome Form [279KB, 4 pages]: Progress information during and post treatment.
Serious Adverse Events : Report life-threatening or serious adverse events associated with TPOXX by completing a PDF MedWatch Form [226KB, 3 pages] and returning it to CDC via email (regaffairs@cdc.gov) or uploading to ShareFile within 72 hours of awareness or sooner, if possible. The PDF MedWatch Form can also be downloaded from the FDA website. (Note: The MedWatch Form can only be viewed on the Adobe desktop app. Please save or download the form for viewing.)
Optional Photos and Samples
Photos of lesions: If feasible, take lesion photos at baseline prior to TPOXX treatment, and post-treatment to follow lesion progression and healing during treatment.
Lesions samples for resistance testing: Ideally, a sample from at least 1 lesion prior to TPOXX treatment but only if baseline diagnostic testing wasn’t performed, as well as samples from any new lesions that develop during and after TPOXX treatment to assess for development of antiviral resistance mutations. See Optional Lesion Samples for Resistance Testing [117KB, 1 page] for instructions on collection, storage, and submission of samples.
Pharmacokinetic samples for testing: During TPOXX treatment, plasma samples may be collected to monitor TPOXX levels for adequate drug exposure in patients. See Optional Pharmacokinetic Samples for Testing [253KB, 5 pages] for instructions on collection, storage, and submission of samples.
My experience is that most busy, overwhelmed physicians are going to find a reason not to prescribe this potentially helpful, but unapproved, drug based on these burdensome administrative requirements. All of us would probably agree on the need for data collection during the novel treatment of human Monkeypox with this drug, but alleviation of suffering should also figure into the governmental response.
This is the prediction portion, and to be taken with a grain of salt. TPOXX is a bit unusual in the antiviral drug world. Most antivirals work by inhibiting the action of some critical enzyme in the life cycle of the virus, and thus preventing replication of new virions. Blocking attachment or entry of the virus to uninfected cells is another strategy. TPOXX works at the very last stage of the virus life cycle, where the completed virus is wrapped in several layers of a lipid envelope before fusing with the human cell membrane and being released. I bet we will find virological relapse after completion of therapy and clinical improvement in Monkeypox, similar to Paxlovid relapse. When it comes to this prediction the old adage, “like shooting fish in a barrel”, seems to apply. (Frankly I never really understood that saying, it always seemed to me after the first couple shots the barrel would be full of holes and you could just pick up the fish and save your ammo… in case you needed it to defend Taiwan).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663070/
The second prediction involves the newer Omicron variant BA. 2.75 which I touched on recently. This variant is spreading explosively in India and has been reported from over 25 countries and now 10 US states. The good news from India is that it does not appear to be leading to a surge in hospitalizations. A recent preprint from David Ho’s lab shows that although this variant, with a number of concerning novel mutations, shows increased immune evasion compared to BA.2, it does not show significantly more vaccine evasion than BA.5, and does not significantly escape from the antibodies contained in the serum of people recovered from BA.4/.5. While India had a massive Delta wave, it did not have a very large BA.4/.5 surge; on the other hand BA.4/.5 is running through our population like coyote in a rabbit hutch. The prediction is obvious: BA.2.75 is not destined to be the next big COVID thing here. Three grains of salt and I’m done for today.
Have a great summer weekend, hope it’s cooler in your neck of the woods. Thanks for your time. Try and share this with at least one friend or colleague.